519P - FOLFOXIRI + bevacizumab (BEV) in patients (pts) with previously untreated metastatic colorectal cancer (mCRC): Final survival and pharmacogenomic p...

Date 29 September 2014
Event ESMO 2014
Session Poster Display session
Topics Anticancer Agents
Colon and Rectal Cancer
Biological Therapy
Presenter Alexander Stein
Citation Annals of Oncology (2014) 25 (suppl_4): iv167-iv209. 10.1093/annonc/mdu333
Authors A. Stein1, D. Atanackovic2, J. Stoehlmacher3, B. Hildebrandt4, P. Stübs5, C. Steffens6, W. Brugger7, G. Hapke8, G. Illerhaus9, E. Bluemner10, C. Bokemeyer11
  • 1University Cancer Center Hamburg Department Of Oncology/haematology, University Medical Center Hamburg-Eppendorf, 20246 - Hamburg/DE
  • 2Division Of Hematology And Hematologic Malignancies, University of Utah, 84112 - Salt Lake City/US
  • 3Tumorgenetik Bonn, Kooperation für Tumordiagnostik, 5311 - Bonn/DE
  • 4Klinik Mit Schwerpunkt Hämatologie Und Onkologie, Charite, DE-13353 - Berlin/DE
  • 5Department Of General, Visceral And Vascular Surgery, Otto-von-Guericke University Magdeburg, Magdeburg/DE
  • 6Dep. For Oncology/hematology, MVZ Haematologie/Onkologie Klinik Dr. Hancken, Stade/DE
  • 7Hematology/oncology, Schwarzwald Baar Klinikum Villingen-Schwenning, DE-78050 - Villingen-Schwenningen/DE
  • 8Dep. For Oncology/hematology, Marienkrankenhaus, Hamburg/DE
  • 9Dep. For Oncology/hematology, Klinikum Stuttgart, Stuttgart/DE
  • 10Biostatistics, ECRON ACUNOVA, Munich/DE
  • 11Dept. Hemato/oncology, UKE II. Medizinische Klinik und PoliklinikMedizinische Klinik II., 20246 - Hamburg-Eppendorf/DE



The addition of BEV to standard doublet chemotherapy (CT) improves outcomes vs CT alone in pts with mCRC. Use of more intensive triplet CT may prolong overall survival (OS), progression-free survival (PFS), increase response rates and improve resectability rates but at the expense of greater toxicity. The OPAL study examined the effect of BEV + FOLFOXIRI on PFS in pts with previously untreated unresectable mCRC. Here we report final survival and pharmacogenetic results.


Eligible pts had histologically confirmed mCRC, ECOG PS ≤1 and were 18–70 years old. Pts received ≤12 cycles of FOLFOXIRI (infusional 5-fluorouracil [FU] 3200 mg/m2, folinic acid [FA] 200 mg/m2, oxaliplatin 85 mg/m2 and irinotecan 165 mg/m2) + BEV 5 mg/kg q2w (induction phase) followed by ≤40 cycles of 5-FU/FA + BEV q2w (maintenance phase). PFS was the primary endpoint; secondary endpoints included OS, proportion of pts achieving resectability, safety, and prognostic value of pharmacogenetic profiling (single nucleotide polymorphisms (SNP) for VEGF-A, VEGFR 1-3, PDGFR beta, HIF 1 alpha, Neuropilin).


96 pts were enrolled. Of these, 90 received study medication and formed the safety population: 64 male, 26 female; median age 58 (range 28–71) years; ECOG performance status 0/1 in 49/41 pts; liver only disease in 35 pts. During induction phase a median number of 9.5 cycles FOLFOXIRI and BEV was administered. Relative dose intensities were 81-86% for all 4 drugs. The incidence of adverse events (AEs) was as previously reported and there were no new safety signals. during induction phase. In total, 61 serious AEs occurred in 34 pts (38%). AEs resulting in death occurred in 3 pts (3%); these were not considered treatment-related by the investigators. Median PFS was 11.1 months (m) (95% CI 9.4-12.0) and OS was 32.2m (95% CI 22.6-36.9). 52 pts were pharmacogenetically profiled and VEGFR 2 SNP 305 was associated with OS (CC–12.4m, CT–18.7m, and TT–30.1m; p = 0.038).


FOLFOXIRI + BEV was feasible in this mCRC pt population. Survival was relevantly increased compared to standard three drug combinations in a molecularly unstratified pt population. VEGFR 2 SNPs might be prognostic for treatment with FOLFOXIRI + BEV.


A. Stein: Roche: membership on an advisory board, corporate-sponsored research. C. Bokemeyer: Roche: corporate-sponsored research. All other authors have declared no conflicts of interest.